In recent years, dry eye patients have been increased with spread of a contact lens and increase in a VDT-operation. Dry eye is a disease exhibiting symptoms such as xerophthalmia, corneal afflux, foreign body feeling, itching feeling and the like, which results in corneal disorders, in principal, due to lowered lacrimal secretion. In addition, it is said that when dry eye becomes severe, it also causes paropsia and asthenopia.
It is believed as a cause of lowered lacrimal secretion, there are Riley-day syndrome, Shy-Drager syndrome, Sjögren's syndrome, sarcoidosis, amyloidosis, sequela of radiotherapy, lagophthalmos, vitamin A deficiency, Stevens-Johnson syndrome, occular pemphigoid, blepharitis marginal, meibomitis, sequela of intraoccular surgery, contact lens disorder; diabetic ectocorneal disease, VDT-operation, driving over a long period of time and the like (see, PROGRESS IN MEDICINE, 26(4):853-856, 2006, REFRACTORY DISEASES AND HOME-CARE, 9(12):61-64, 2004 and JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 199(5):387-392, 2001, for Sjögren's syndrome and a method for treatment thereof).
The lacrimal fluid exists in a border portion where an eyeball contacts with air, and constitutes a thin fluid layer having a thickness of approximately 7 μm which covers an outermost layer of the eyeball. The lacrimal fluid has a three-layered structure, which consists of, from an outer side, an oily layer, an aqueous layer and a mucinous layer, and each layer plays an important role in preventing the eyeball from dryness. The aqueous layer, which occupies most of the lacrimal fluid thickness, is prevented from the decrement by existing between the oily layer and the mucinous layer to maintain the wettability of the eyeball. The oily layer is in principle secreted from a gland existing around an eyelid, which is called meibom gland, and prevents moisture from evaporation by covering throughout the aqueous layer. Accordingly, when the production of the oily layer is reduced due to meibomitis, the aqueous layer becomes apt to evaporate and, thereby, symptom of dry eye is exhibited. The mucinous layer covers a hydrophobic ectocorneal surface to change the surface to hydrophilic and, thereby, has the function of retaining the aqueous layer on an ectocorneal, surface.
The lacrimal fluid has various functions in addition to prevention of dry eye. Other functions of the lacrimal fluid include, for example, protection of cornea and conjunctiva, bacteriostatic action, prevention of infection with bacteria, fungus, virus and the like, feeding of oxygen and a variety of nutritions to cornea and removal of a carbon dioxide gas and metabolites therefrom, dilution and removal of harmful stimuli in the case where cornea and conjunctiva injured, transportation of liquid components such as epidermal growth factors which participate in wound healing and the like and hematocyte components such as fibronectin and the like to the injured portion, retainment of cornea and a conjunctival epithelial cell, regulation of wound healing and the like.
At present, various artificial lacrimal fluid-type eye drops have been sold for the purpose of treatment of lowered lacrimal secretion. However, many of them are a preparation comprising inorganic salts and/or metal chelating agents for the purpose of supplementing the lacrimal fluid and, therefore, although they are temporarily effective to solve the dry feeling of eye followed by lowered lacrimal secretion, the effect is not sustained because they do not affect lacrimal secretion itself. In addition, it is difficult to persistently remove unpleasantnesses such as foreign body feeling and itching upon wearing the contact lens, burning feeling of eye and the like due to dry eye. Furthermore, when those having a lowered amount of oily secretion from meibom gland increase a frequency of the treatment with eye drops, dry feeling of eye becomes stronger due to washing out of the oily and mucinous layers. This attributes to the problem due to a lacrimal fluid components supplementing therapy, but not a lacrimal secretion promoting therapy, which increases lacrimal secretion itself.
As stated above, ophthalmologists and dry eye patients have desired development of a composition for promoting lacrimal secretion which can be used safely and effectively in the lacrimal secretion promoting therapy, not in the conventional lacrimal fluid components supplementing therapy.
For example, JP 2001-181208A discloses an invention in which an peptide having an amino acid sequence: Ser-Leu-Ile-Gly-Arg-Leu-NH2 activates PAR-2 which is a subtype of PAR (Protease-activated receptor) and consequently promoting lacrimal secretion.
In addition, JP 2001-181208A discloses a composition comprising a peptide component consisting of sequential three or four kinds of amino acid of isoleucine (Ile), glycine (Gly), arginine (Arg) and leucine (Leu) as an active center of an excellent lacrimal secretion promoting action.